Exercise in MPNs: a promising first step

In this issue of Blood Advances, Ouellet et al¹ conducted a pilot randomized controlled trial of a supervised exercise program (FIT) in patients with myeloproliferative neoplasms (MPNs), evaluating FIT’s feasibility and acceptability and exploring its preliminary efficacy in improving symptoms, quality of life (QOL), and disease and inflammatory biomarkers.

A total of 55 patients with MPN were randomized 3:2 to the FIT intervention or control arm; MPN disease subtypes and median participant age were overall representative of the broader MPN population. The FIT intervention consisted of a home- and group-based program developed by a certified kinesiologist to align with each patient’s baseline abilities and preferences, and incorporated flexibility, balance, resistance, and aerobic training. Participants were encouraged to gradually increase their aerobic activity, with a goal of reaching 150 to 300 minutes per week and received follow-up sessions with the kinesiologist to help meet this target. In contrast, control patients were instructed to maintain their usual physical activity level for 12 weeks, after which they were offered an optional exercise program similar to FIT. Unsurprisingly, FIT resulted in a substantial increase in physical activity, with participants completing 1280 minutes of activity over the 12 weeks compared with 120 minutes in the control arm.

The program was well-received, and all prespecified feasibility benchmarks were met: 80% of FIT participants endorsed satisfaction with the intervention, and >90% expressed intent to continue exercising after the study period. Although no significant differences in patient-reported outcomes (PROs) were detected between groups, participants randomized to FIT described meaningful health benefits in qualitative interviews. Intriguingly, FIT was associated with a significant reduction in lactate dehydrogenase (LDH) levels compared to controls, although no other inflammatory markers differed significantly.

Few ideas in medicine are as universally accepted as the truism that exercise is good for you. The challenge now however, lies in determining how to leverage and measure the benefits of exercise, and how to get patients to exercise. In the general cancer population, there is a plethora of data demonstrating the positive impact of structured exercise on fatigue, symptoms, anxiety, and QOL.² The effects of exercise on chronic inflammation and immunity also raise the tantalizing prospect of disease modification, as highlighted by a recent phase 3 trial showing improved disease-free survival with a 3-year structured exercise program in colon cancer survivors after adjuvant chemotherapy.³

In MPNs, the rationale for exercise is particularly compelling. Cardiovascular events are the leading cause of morbidity and mortality,⁴ and exercise, along with diet, is a key modifiable determinant of cardiovascular risk. Moreover, the relatively long survival of many patients with MPN and the scarcity of disease-modifying therapies make supportive, sustainable approaches such as exercise appealing for MPN management—both as a means of patient empowerment and as a long-term approach to mitigating cumulative health risks. Lifestyle interventions targeting inflammation are particularly relevant in MPNs, as inflammation drives both symptoms and disease progression; in addition to exercise, anti-inflammatory dietary interventions are being investigated in MPNs, including a recent randomized trial evaluating the impact of adopting a Mediterranean diet.⁵

Despite this strong theoretical foundation, studies of exercise in MPNs have been limited. Retrospective survey studies have shown associations between exercise and lower fatigue in MPNs,^6,7 and a pilot, online yoga study demonstrated small effects in anxiety, depression, sleep, and pain.⁸ A single-arm, exercise-based rehabilitation intervention incorporating aerobic and strength training found improvement in physical capacity and no changes in fatigue or QOL⁹; however, the intervention was limited by patients’ poor adherence (34%) to training sessions. MPN-FIT is the first randomized controlled trial of a supervised exercise intervention in MPNs and represents an important advance in this area. It introduces a more comprehensive regimen incorporating aerobic, balance, and resistance training with excellent feasibility and acceptability. The results provide the necessary groundwork for larger studies capable of evaluating efficacy more definitively and for future recommendations regarding how to integrate exercise into standard MPN care. The study’s biologic findings, including decreased LDH and a trend toward lower inflammatory markers in FIT participants, warrant further mechanistic work. As a pilot trial, this study is not designed to establish a definitive role for exercise in reducing inflammation or modifying disease biology in MPNs, and future studies need more hypothesis-driven conceptualizations of how exercise can impact inflammation and downstream outcomes, with deliberately chosen biomarkers to clarify the expected biological effects. This pilot study also informs the design of future interventions, with qualitative interviews highlighting factors that appeared to facilitate engagement. Given the wide and still largely untapped potential for lifestyle-based interventions in MPNs, these insights are especially valuable and underscore the importance of incorporating mixed-methods approaches in early-phase studies to better understand feasibility and patient experience.

Several challenges remain. The intervention was resource-intensive, requiring a trained kinesiologist in small-group sessions and substantial participant support, and it was time-limited with unclear effects on durability. Whether such an intervention is scalable to a broader MPN population while still maintaining efficacy for its proposed outcomes remains to be seen. Although enrollment was consecutive, a third of patients declined participation prior to eligibility screening, raising questions about generalizability. PROs including MPN symptom scores also remained similar between FIT and control groups, perhaps related to contamination; however, this still raises questions about what types of exercise programs are most beneficial for patients with MPNs and how we choose our PROs to measure these benefits. Ultimately, the study highlights 2 conceptually distinct areas that future work will need to disentangle: (1) the extent to which higher-intensity or higher-dose exercise can reduce inflammation or influence MPN disease biology, and (2) how best to design pragmatic interventions that increase physical activity across the heterogenous MPN population, and what clinical or symptomatic benefits such increased activity can confer.

MPN-FIT suggests that supervised exercise is feasible, welcomed by patients, and with signals for physical, psychological, and possibly biological benefits. It lays an important foundation for future studies aimed at defining the role of lifestyle modification in improving the lives of patients with MPNs.

Conflict-of-interest disclosure: The author declares no competing financial interests.